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Tubular epithelial cells (TEC), the major component of kidney parenchyma, are vulnerable to different types of injuries and are a significant source of myofibroblast by EMT. Furthermore, TRPC6 knockout plays an anti-fibrotic role in ameliorating kidney damage. However, the relationship between TRPC6 and EMT is unknown. In this study, TRPC6<jats:sup>\u2212\/\u2212<\/jats:sup>and wild-type (WT) mice were subjected to a unilateral ureteric obstruction (UUO) operation. Primary TEC were treated with TGF-\u03b21. Western blot and immunofluorescence data showed that fibrotic injuries alleviated with the inhibition of EMT in TRPC6<jats:sup>\u2212\/\u2212<\/jats:sup>mice compared to WT mice. The activation of AKT-mTOR and ERK1\/2 pathways was down-regulated in the TRPC6<jats:sup>\u2212\/\u2212<\/jats:sup>mice, while the loss of Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup>-ATPase and APQ1 was partially recovered. We conclude that TRPC6 knockout may ameliorate kidney fibrosis by inhibition of EMT through down-regulating the AKT-mTOR and ERK1\/2 pathways. This could contribute to the development of effective therapeutic strategies on chronic kidney diseases.<\/jats:p>","DOI":"10.3389\/fcell.2020.602703","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T05:09:06Z","timestamp":1610687346000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Transient Receptor Potential Channel 6 Knockout Ameliorates Kidney Fibrosis by Inhibition of Epithelial\u2013Mesenchymal Transition"],"prefix":"10.3389","volume":"8","author":[{"given":"Yanhong","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anbang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qifang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenzhu","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xixi","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhong","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3151","DOI":"10.1242\/dev.01907","article-title":"The Snail genes as inducers of cell movement and survival: implications in development and cancer","volume":"132","author":"Barrallo-Gimeno","year":"2005","journal-title":"Development"},{"key":"B2","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1038\/nm.2135","article-title":"Methylation determines fibroblast activation and fibrogenesis in the kidney","volume":"16","author":"Bechtel","year":"2010","journal-title":"Nat. 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